Lithium diisopropylamide → 1-(5-(4-Bromo-3,5-dimethoxyphenyl)furan-2-yl)-2-methoxy-2-(4-morpholinophenyl)ethanone

HRID 56506Notes

Reaction equation

HRID 56506 reaction equation
[Br:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]2[O:11][CH:12]=[CH:13][CH:14]=2)=[CH:4][C:3]=1[O:15][CH3:16].C([N-]C(C)C)(C)C.[Li+].CON(C)[C:28](=[O:44])[CH:29]([O:42][CH3:43])[C:30]1[CH:35]=[CH:34][C:33]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)=[CH:32][CH:31]=1>C1COCC1>[Br:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]2[O:11][C:12]([C:28](=[O:44])[CH:29]([O:42][CH3:43])[C:30]3[CH:31]=[CH:32][C:33]([N:36]4[CH2:37][CH2:38][O:39][CH2:40][CH2:41]4)=[CH:34][CH:35]=3)=[CH:13][CH:14]=2)=[CH:4][C:3]=1[O:15][CH3:16]

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 584319882-(4-Bromo-3,5-dimethoxyphenyl)furanHCID 58431993N,2-dimethoxy-N-methyl-2-(4-morpholinophenyl)acetamide

Product 1

HCID 584320731-(5-(4-Bromo-3,5-dimethoxyphenyl)furan-2-yl)-2-methoxy-2-(4-morpholinophenyl)ethanoneYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-(4-bromo-3,5-dimethoxyphenyl)furan (0.203 g, 0.72 mmol) in anhydrous THF (2 mL) under argon in an oven-dried flask cooled to −78° C. was added a solution of lithium diisopropylamide (2.0 M in THF/heptane/ethylbenzene; 0.4 mL, 0.8 mmol) dropwise. After stirring for 35 min at −78° C., a solution of N,2-dimethoxy-N-methyl-2-(4-morpholinophenyl)acetamide (0.315 g, 1.1 mmol) in THF (2 mL) was added dropwise. After stirring for 25 min, the mixture was allowed to warm to room temp while stirring for 2 hrs. The reaction was quenched with the addition of saturated aqueous NH4Cl then brine and EtOAc were added. The layers were separated and the organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. Purification by column chromatography (35-65% EtOAc-hexanes) provided an oil that was triturated with MeOH-Et2O (1:1) with sonication. The solid was collected on a Büchner, rinsed with MeOH-Et2O (1:1) and dried in vacuo to give 1-(5-(4-bromo-3,5-dimethoxyphenyl)furan-2-yl)-2-methoxy-2-(4-morpholinophenyl)ethanone as a yellow solid. A second batch was collected from MeOH-Et2O (˜10%) to give additional product (0.220 g total, 59% yield). MS: m/z 516.1 [M+H]+.

Workup

  1. stirringAfter stirring for 25 min
  2. temperatureto warm to room temp
  3. stirringwhile stirring for 2 hrs
  4. customThe reaction was quenched with the addition of saturated aqueous NH4Cl
  5. additionbrine and EtOAc were added
  6. customThe layers were separated
  7. washthe organic layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customPurification by column chromatography (35-65% EtOAc-hexanes)
  11. customprovided an oil that
  12. customwas triturated with MeOH-Et2O (1:1) with sonication
  13. customThe solid was collected on a Büchner
  14. washrinsed with MeOH-Et2O (1:1)
  15. customdried in vacuo

Sources & evidence

ORD record
ord-6c2ceb22e8c74632a1aa535eaba0c484
Source dataset
uspto-grants-2016_09
Patent number
US09434707B2

Reaction notes

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